During the past year, we have completed our studies of deoxyribonucleotide metabolism in the cell cycle of S49 lymphoblasts. Our conclusions were that ribonucleotide reductase activity is increased during S phase of the cell cycle, and coincident with this there is an increase in the deoxyribonucleoside triphosphate pools. The pattern of the increase suggested that allosteric regulation of ribonucleotide reductase is in part responsible for the increased pool size but, in addition, there appeared to be a non-allosteric increase in the activity of ribonucleotide reductase. This increased activity is probably due to the increase in M2 activity, although neither of the two subunits M1 nor M2, as evaluated by two-dimensional electrophoresis, appears to increase in quantity during S phase. Further studies are now in progress to ascertain whether the same patterns hold for a line of hydroxyurea-resistant cells, which are tentatively identified as being amplified in the M2 subunit of ribonucleotide reductase, and thus have increased amounts of deoxyribonucleoside triphosphates and increased ribonucleotide reductase activity. (N)